Crossveinless-c, the Drosophila homolog of tumor suppressor DLC1, regulates directional elongation of dendritic branches via down-regulating Rho1 activity.

Laboratory of Cell Recognition and Pattern Formation, Graduate School of Biostudies, South Campus Research Building (Building G), Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Genes to Cells (Impact Factor: 2.86). 04/2010; 15(5):485-500. DOI: 10.1111/j.1365-2443.2010.01399.x
Source: PubMed

ABSTRACT Diverse neuronal subtypes develop distinctive morphologies of dendritic arbors that receive synaptic or sensory inputs. Dendritic arbors of many subtypes take on a polarized shape, and one underlying mechanism is unidirectionally biased elongation of dendritic branches. As reported herein, we found that Drosophila Crossveinless-c (Cv-c) was a key regulator for such directional growth. In the cv-c mutant, two subclass of multidendritic sensory neurons examined formed dorsally directed branches; however, dendritic branches had difficulty in growing along the anterior-posterior (A-P) body axis. Cv-c belongs to the family of Rho GTPase-activating proteins (RhoGAPs) and is the homolog of human tumor suppressor DLC1. The RhoGAP activity of Cv-c was required cell-autonomously for the A-P-oriented growth, and Cv-c elevated the GTPase activity of Rho1 and Cdc42 in a cell-free assay. Our analysis of genetic interactions suggested that Rho1 was the target of Cv-c in vivo. All of our results suggest that Cv-c contributes to sprouting and subsequent growth of the A-P-oriented branches through negative regulation of Rho1. We discuss a role of Cv-c in dendritic growth in response to environmental cues.

1 Follower
  • Source
    Edited by Yue Cheng, 04/2013; InTech., ISBN: 978-953-51-1063-7
  • [Show abstract] [Hide abstract]
    ABSTRACT: Duchenne muscular dystrophy is caused by mutations in the Dystrophin gene and is characterized by muscle degeneration and the occurrence of mental deficits in a significant number of patients. Although Dystrophin and its closely related ortholog Utrophin are present at a variety of synapses, little is known about their roles in the nervous system. Previously, we reported that absence of postsynaptic Dystrophin from the Drosophila neuromuscular junction (NMJ) disrupts synaptic homeostasis, resulting in increased stimulus-evoked neurotransmitter release. Here, we show that RhoGAP crossveinless-c (cv-c), a negative regulator of Rho GTPase signaling pathways, genetically interacts with Dystrophin. Electrophysiological characterization of the cv-c-deficient NMJ and the use of presynaptic- and postsynaptic-specific transgenic rescue versus RNA interference reveal that the absence of postsynaptic cv-c results in elevated evoked neurotransmitter release. The cv-c mutant NMJ exhibits an increased number of presynaptic neurotransmitter release sites and higher probability of vesicle release without apparent changes in postsynaptic glutamate receptor numbers or function. Moreover, we find that decreasing expression of the Rho GTPase Cdc42 suppresses the high neurotransmitter release in the cv-c and Dystrophin mutants, suggesting that Cdc42 is a substrate of Cv-c. These results indicate that Dystrophin and the Rho GTPase signaling pathway likely interact at the postsynaptic side of the NMJ to maintain synaptic homeostasis. The absence of this postsynaptic pathway results in presynaptic structural and functional alterations, suggesting that retrograde signaling mechanisms are affected.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 01/2011; 31(2):492-500. DOI:10.1523/JNEUROSCI.4732-10.2011 · 6.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Most organs scale proportionally with body size through regulation of individual cell size and/or cell number. Here we addressed how postmitotic and morphologically complex cells such as neurons scale with the body size by using the dendritic arbor of one Drosophila sensory neuron as an assay system. In small adults eclosed under a limited-nutrition condition, the wild-type neuron preserved the branching complexity of the arbor, but scaled down the entire arbor, making a "miniature". In contrast, mutant neurons for the Insulin/IGF signaling (IIS) or TORC1 pathway exhibited "undergrowth", which was characterized by decreases in both the branching complexity and the arbor size, despite a normal diet. These contrasting phenotypes hinted that a novel regulatory mechanism contributes to the dendritic scaling in wild-type neurons. Indeed, we isolated a mutation in the gene CHORD/morgana that uncoupled the neuron size and the body size: CHORD mutant neurons generated miniature dendritic arbors regardless of the body size. CHORD encodes an evolutionarily conserved co-chaperone of HSP90. Our results support the notion that dendritic growth and branching are controlled by partly separate mechanisms. The IIS/TORC1 pathways control both growth and branching to avert underdevelopment, whereas CHORD together with TORC2 realizes proportional scaling of the entire arbor.
    Scientific Reports 03/2014; 4:4415. DOI:10.1038/srep04415 · 5.58 Impact Factor